An evaluation of antimicrobial stewardship in community pharmacy

This study investigated several aspects of antimicrobial stewardship by gathering information from community pharmacists and members of the public. The aim was to identify how community pharmacists implement antimicrobial stewardship guidelines and influence patients on the use of antibiotics. This study required and received approval from the University of Huddersfield Ethics Committee. Information and opinions of community pharmacists in the Kirklees and Calderdale areas, and surrounding local areas, and of members of the public in Huddersfield town centre, were gathered using two different questionnaires. These focused on initiatives regarding antibiotic resistance, development of the competencies required for medicines optimisation and antimicrobial stewardship, patient education by pharmacists, monitoring of antibiotic prescribing and pharmacy access to records. The results obtained were then analysed. The study consisted of 50 participating pharmacists and 100 participating members of the public. It was identified that eight pharmacists had undertaken recent professional development regarding antimicrobial stewardship, 11 had made an Antibiotic Guardian pledge and eight monitored antibiotic prescribing. It was also discovered that, when handing out a prescription for antibiotics, five pharmacists (all of whom work in an independent pharmacy) always questioned the indication and seven always provided extra self-care information. Finally, 92 members of the public selected that they would be comfortable allowing their indication (the condition that the antibiotic is being used to treat) to be provided on prescriptions for antibiotics, and 83 selected that they would be comfortable with pharmacies having access to medical records. This study suggests that increased awareness is necessary of the resources that are available to pharmacists regarding antibiotic resistance initiatives and monitoring of antimicrobial prescribing. In addition, an improvement is required concerning patient education by community pharmacists. Finally, the public should be appropriately educated regarding patient confidentiality and the benefits of pharmacies having access to patient information

Assessment of Methods for the Intracellular Blockade of GABAA Receptors

Selective blockade of inhibitory synaptic transmission onto specific neurons is a useful tool for dissecting the excitatory and inhibitory synaptic components of ongoing network activity. To achieve this, intracellular recording with a patch solution capable of blocking GABAA receptors has advantages over other manipulations, such as pharmacological application of GABAergic antagonists or optogenetic inhibition of populations of interneurones, in that the majority of inhibitory transmission is unaffected and hence the remaining network activity preserved. Here, we assess three previously described methods to block inhibition: intracellular application of the molecules picrotoxin, 4,4'-dinitro-stilbene-2,2'-disulphonic acid (DNDS) and 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS). DNDS and picrotoxin were both found to be ineffective at blocking evoked, monosynaptic inhibitory postsynaptic currents (IPSCs) onto mouse CA1 pyramidal cells. An intracellular solution containing DIDS and caesium fluoride, but lacking nucleotides ATP and GTP, was effective at decreasing the amplitude of IPSCs. However, this effect was found to be independent of DIDS, and the absence of intracellular nucleotides, and was instead due to the presence of fluoride ions in this intracellular solution, which also blocked spontaneously occurring IPSCs during hippocampal sharp waves. Critically, intracellular fluoride ions also caused a decrease in both spontaneous and evoked excitatory synaptic currents and precluded the inclusion of nucleotides in the intracellular solution. Therefore, of the methods tested, only fluoride ions were effective for intracellular blockade of IPSCs but this approach has additional cellular effects reducing its selectivity and utility

Memory trace replay:The shaping of memory consolidation by neuromodulation

The consolidation of memories for places and events is thought to rely, at the network level, on the replay of spatially tuned neuronal firing patterns representing discrete places and spatial trajectories. This occurs in the hippocampal-entorhinal circuit during sharp wave ripple events (SWRs) that occur during sleep or rest. Here, we review theoretical models of lingering place cell excitability and behaviorally induced synaptic plasticity within cell assemblies to explain which sequences or places are replayed. We further provide new insights into how fluctuations in cholinergic tone during different behavioral states might shape the direction of replay and how dopaminergic release in response to novelty or reward can modulate which cell assemblies are replayed

‘Edible seaweeds’ as an alternative to animal-based proteins in the UK: Identifying product beliefs and consumer traits as drivers of consumer acceptability for macroalgae

Edible macroalgae (i.e., ‘seaweeds’) are a nutritious and sustainable alternative to animal-based proteins. However, consumption of seaweeds in Western countries remains low, and little is known about individual drivers of acceptance. The aim of this study was to further explore the consumer acceptability of seaweed-based food products in the UK. In an online study (N = 476), participants were presented with a general description of edible seaweeds, and descriptions of seaweed-based food products (e.g., ‘seaweed burger’). Participants were asked to rate beliefs about product attributes, and reported acceptance in terms of liking, willingness to try, willingness to buy, and readiness to adopt as a meat alternative. It was predicted that positive beliefs about seaweed-based products would be significantly associated with greater acceptance, and that seaweed-based products would be more favourable than a general description of seaweeds. Supporting study hypotheses, structural equation modelling showed that positive beliefs about taste/ edibility and familiarity significantly predicted acceptance (p .05). These results support the consumer acceptance of seaweeds, and identify scope for utilising specific attributes of seaweeds (as drivers of acceptance) in future product development

Location of the Polyamine Binding Site in the Vestibule of the Nicotinic Acetylcholine Receptor Ion Channel

To map the structure of a ligand-gated ion channel, we used the photolabile polyamine-containing toxin MR44 as photoaffinity label. MR44 binds with high affinity to the nicotinic acetylcholine receptor in its closed channel conformation. The binding stoichiometry was two molecules of MR44 per receptor monomer. Upon UV irradiation of the receptor-ligand complex, (125)I-MR44 was incorporated into the receptor alpha-subunit. From proteolytic mapping studies, we conclude that the site of (125)I-MR44 cross-linking is contained in the sequence alpha His-186 to alpha Leu-199, which is part of the extracellular domain of the receptor. This sequence partially overlaps in its C-terminal region with one of the three loops that form the agonist-binding site. The agonist carbachol and the competitive antagonist alpha-bungarotoxin had only minor influence on the photocross-linking of (125)I-MR44. The site where the hydrophobic head group of (125)I-MR44 binds must therefore be located outside the zone that is sterically influenced by agonist bound at the nicotinic acetylcholine receptor. In binding and photocross-linking experiments, the luminal noncompetitive inhibitors ethidium and triphenylmethylphosphonium were found to compete with (125)I-MR44. We conclude that the polyamine moiety of (125)I-MR44 interacts with the high affinity noncompetitive inhibitor site deep in the channel of the nicotinic acetylcholine receptor, while the aromatic ring of this compound binds in the upper part of the ion channel (i.e. in the vestibule) to a hydrophobic region on the alpha-subunit that is located in close proximity to the agonist binding site. The region of the alpha-subunit labeled by (125)I-MR44 should therefore be accessible from the luminal side of the vestibule

Characteristics of Harmful Text: Towards Rigorous Benchmarking of Language Models

Large language models produce human-like text that drive a growing number of applications. However, recent literature and, increasingly, real world observations, have demonstrated that these models can generate language that is toxic, biased, untruthful or otherwise harmful. Though work to evaluate language model harms is under way, translating foresight about which harms may arise into rigorous benchmarks is not straightforward. To facilitate this translation, we outline six ways of characterizing harmful text which merit explicit consideration when designing new benchmarks. We then use these characteristics as a lens to identify trends and gaps in existing benchmarks. Finally, we apply them in a case study of the Perspective API, a toxicity classifier that is widely used in harm benchmarks. Our characteristics provide one piece of the bridge that translates between foresight and effective evaluation.Comment: Accepted to NeurIPS 2022 Datasets and Benchmarks Track; 10 pages plus appendi

The 2020 release of the ExoMol database:Molecular line lists for exoplanet and other hot atmospheres

The ExoMol database (www.exomol.com) provides molecular data for spectroscopic studies of hot atmospheres. While the data is intended for studies of exoplanets and other astronomical bodies, the dataset is widely applicable. The basic form of the database is extensive line lists; these are supplemented with partition functions, state lifetimes, cooling functions, Land\'e g-factors, temperature-dependent cross sections, opacities, pressure broadening parameters, $k$-coefficients and dipoles. This paper presents the latest release of the database which has been expanded to consider 80 molecules and 190 isotopologues totaling over 700 billion transitions. While the spectroscopic data is concentrated at infrared and visible wavelengths, ultraviolet transitions are being increasingly considered in response to requests from observers. The core of the database comes from the ExoMol project which primarily uses theoretical methods, albeit usually fine-tuned to reproduce laboratory spectra, to generate very extensive line lists for studies of hot bodies. The data has recently been supplemented by line lists deriving from direct laboratory observations, albeit usually with the use of ab initio transition intensities. A major push in the new release is towards accurate characterisation of transition frequencies for use in high resolution studies of exoplanets and other bodies